Nucleotide and nucleoside-based drugs: past, present, and future

Abstract

Nucleotide and nucleoside-based analogue drugs are widely used for the treatment of both acute and chronic viral infections. These drugs inhibit viral replication due to one or more distinct mechanisms. It modifies the virus's genetic structure by reducing viral capacity in every replication cycle. Their clinical success has shown strong effectiveness against several viruses, including ebolavirus, hepatitis C virus, HIV, MERS, SARS-Cov, and the most recent emergent SARS-Cov2. In this review, seven different types of inhibitors have been selected that show broad-spectrum activity against RNA viruses. A detailed overview and mechanism of actionof both analogues are given, and the clinical perspectives are discussed. These inhibitors incorporated the novel SARS-CoV-2 RdRp, further terminating the polymerase activity with variable efficacy. The recent study provides a molecular basis for the inhibitory activity of virus RdRp using nucleotide and nucleoside analogues inhibitors. Furthermore, to identify those drugs that need more research and development to combat novel infections. Consequently, there is a pressing need to focus on present drugs by establishing their cell cultures. If their potencies were evidenced, then they would be explored in the future as potential therapeutics for novel outbreaks.

Keywords: Infection; Inhibitors; Nucleoside; Nucleotide; Pandemic; RdRp.

Graphical abstract

Fig. 1

The structure of Remdesivir.

Fig. 2

H-bonding and hydrophobic interactions of Sofosbuvir COVID −19 RdRp.

Fig. 3

The chemical structure of Ribavirin.

Fig. 4

The chemical structure of Galidesivir.

Fig. 5

The chemical structure of Tenofovir.

Fig. 6

The chemical structure of Mizoribine.

Fig. 7

The chemical structure of Favipiravir.